#5476 sex differences in incident kidney failure and the impact of risk factors in a population study

Abstract Background and Aims Chronic kidney disease (CKD) has different effects on women and men. Women are more likely to have CKD, but men are more likely to develop kidney failure requiring treatment (KFRT: dialysis or transplantation). Recent studies have highlighted sex differences in CKD progression and there is a need to determine if this relates to differential effects of risk factors. Method We used primary care data stored within the electronic health records repository Secure Anonymised Information Linkage Databank (SAIL) for adults with CKD stages G3/4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m2) living in Wales, UK. We studied the relationship between sex and the development of kidney failure (KFRT or incident eGFR<15 mL/min/1.73 m2 for ≥3 months). Sex-specific rates of kidney failure were compared using an event plot with patients censored on the date of death. Cox proportional hazards models tested associations between sex and kidney failure, before and after adjustment for other known risk factors (age, baseline eGFR, smoking, social deprivation, diabetes mellitus and hypertension). Interactions between sex and risk factors were sought and interaction terms were retained if these were statistically significant (p-value<0.05). Models were then stratified by sex to compare the impact of risk factors in men and women. Results 135,635 patients (median age 78 years, 57% female, median baseline eGFR 50 mL/min/1.73 m2) were followed up for a median of 6.8 years, representing a total of 782,237 patient years. 1.1% of women and 2.3% of men developed kidney failure. An unadjusted Cox model including both sexes showed a hazard ratio of 2.06 (95% confidence interval 1.89-2.24) for men. After adjustment for all risk factors and inclusion of interaction terms (between sex and baseline eGFR and sex and age), men were not more likely to develop kidney failure (aHR 0.91, 0.60-1.38) (Figure 1A). In sex-stratified models, kidney failure was most likely to develop in those with low baseline eGFR, younger age, current and ex-smokers, patients with diabetes mellitus and patients with hypertension (Figure 1B). Diabetes was a more important risk factor for kidney failure in women (aHR in women 1.73 (1.51-1.98) compared with men (aHR 1.56, 1.39-1.74). Hazard ratios for other risk factors were similar in men and women. Conclusion We found that sex differences in rates of kidney failure are related to a differential impact of risk factors – in particular diabetes – on CKD progression. These results warrant further investigation with a need to determine whether risk reduction strategies should be different in men and women with CKD, or whether current diagnosis, monitoring and treatment strategies are either applied differentially or have different benefit and harms by sex.